Rad51-dependent DNA structures accumulate at damaged replication forks in <i>sgs1</i> mutants defective in the yeast ortholog of BLM RecQ helicase

Liberi, Giordano; Maffioletti, Giulio; Lucca, Chiara; Chiolo, Irene; Baryshnikova, Anastasia; Cotta‐Ramusino, Cecilia; Lopes, Massimo; Pellicioli, Achille; Haber, James E.; Foiani, Marco

doi:10.1101/gad.322605

Cited by 295 publications

(385 citation statements)

References 86 publications

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“…In addition to the loss of cell cycle checkpoint function [71], the loss of Sgs1 or Top3 increases sister chromatid exchange rate and HR [72]. Similar to the mms21-11 mutation, the sgs1 mutation accumulates pseudo-dHJ like structures upon exposure to the DNA damaging agent methylmethane sulfonate [33,57]. We found synergistic increases of GCR rates by either the sgs1 or top3 mutation with the smc6-9 mutation (Table 5).…”

Section: Discussionmentioning

confidence: 67%

“…The inactivation of Mms21, a protein in the Smc5-Smc6 complex results in the accumulation of X molecules [33] that resemble pseudo-double Holliday junctions (dHJs) or hemicatenanelike molecules, and they occur specifically when forks encounter a damaged template [57]. Cells lacking the helicase Sgs1 or Topoisomerase III also accumulate these pseudo-dHJs.…”

Section: Inactivation Of Dna Damage Checkpoints In the Smc6-9 Strain mentioning

confidence: 99%

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Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

et al. 2008

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Translocations in chromosomes alter genetic information. Although the frequent translocations observed in many tumors suggest the altered genetic information by translocation could promote tumorigenesis, the mechanisms for how translocations are suppressed and produced are poorly understood. The smc6-9 mutation increased the translocation class gross chromosomal rearrangement (GCR). Translocations produced in the smc6-9 strain are unique because they are nonreciprocal and dependent on break-induced replication (BIR) and independent of non-homologous end joining. The high incidence of translocations near repetitive sequences such as δ sequences, ARS, tRNA genes, and telomeres in the smc6-9 strain indicates that Smc5-Smc6 suppresses translocations by reducing DNA damage at repetitive sequences. Synergistic enhancements of translocations in strains defective in DNA damage checkpoints by the smc6-9 mutation without affecting de novo telomere addition class GCR suggest that Smc5-Smc6 defines a new pathway to suppress GCR formation.

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Section: Discussionmentioning

confidence: 67%

Section: Inactivation Of Dna Damage Checkpoints In the Smc6-9 Strain mentioning

confidence: 99%

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

et al. 2008

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“…(a) (i) Diagram depicting the DNA replication intermediates that can be detected using neutral-neutral 2D gel electrophoresis of a defined restriction fragment. X-shaped DNA molecules may either comprise Rad51-independent sister chromatid junctions 21 or Rad51-dependent homologous recombination intermediates 41 .…”

Section: Tus-ter Modules Cause Polar Rf Pausing In Yeast the 21-bpmentioning

confidence: 99%

“…The sgs1 X-structure arising as a consequence of RF arrest at Tus-Ter modules is highly reminiscent of the post-replicative X-structures that persists in sgs1 mutants following exposure to the replication-perturbing agent, methylmethanesulphonate (MMS) 41,42 . This X-structure does not arise in hydroxyureatreated sgs1 cells 41 , suggesting that it is not a general property of DNA replication stress, but rather arises in response to certain kinds of DNA replication impediments.…”

Section: Tus-ter Modules Cause Polar Rf Pausing In Yeast the 21-bpmentioning

confidence: 99%

The Escherichia coli Tus–Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

et al. 2014

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Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus, to specific DNA sequences called Ter. Here, we demonstrate that Tus-Ter modules also induce polar RF pausing when engineered into the Saccharomyces cerevisiae genome. This heterologous RF barrier is distinct from a number of previously characterized, protein-mediated, RF pause sites in yeast, as it is neither Tof1-dependent nor counteracted by the Rrm3 helicase. Although the yeast replisome can overcome RF pausing at Tus-Ter modules, this event triggers site-specific homologous recombination that requires the RecQ helicase, Sgs1, for its timely resolution. We propose that Tus-Ter can be utilized as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications.

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“…In particular, Sgs1 and Top3 are suggested to resolve recombination structures originating from sister chromatid junctions at damaged replication forks, while Srs2 prevents their formation (Liberi et al, 2005;Mankouri and Hickson, 2006;Mankouri et al, 2007). mph1 mutants are not deficient in HR, as determination of spontaneous mitotic recombination rates demonstrated.…”

Section: Mph1 Probably Acts At a Stage After Initiation Of Recombinationmentioning

confidence: 99%

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

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Schildmann

et al. 2009

Yeast

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In yeast as in human, DNA helicases play critical roles in assisting replication fork progression. The Saccharomyces cerevisiae MPH1 gene, homologue of human FANCM, has been involved in homologous recombination and DNA repair. We describe a synthetic growth defect of an mph1 deletion if combined with an srs2 deletion that can result -depending on the genetic background -in synthetic lethality. The lethality is suppressed by mutations in homologous recombination (rad51, rad52, rad55, rad57 ) and in the DNA damage checkpoint (rad9, rad24, rad17 ). Importantly, rad54 and mph1, epistatic for damage sensitivity, are subadditive for spontaneous mutator phenotype. Therefore, Mph1 could be placed at the Rad51-mediated strand invasion process, with a function distinct from Rad54. Moreover, siz1 mutation is viable with mph1 and additive for DNA damage sensitivity. mph1 srs2 double mutants, isolated in a background where they are viable, are synergistically sensitive to DNA damage. Moderate overexpression of SGS1 partially suppresses this sensitivity. Finally, we observe an epistatic relationship in terms of sensitivity to camptothecin of mms4 or mus81 to mph1. Overall, our results support a role of Mph1 in assisting replication progression. We propose two models for the resumption of DNA synthesis under replicative stress where Mph1 is placed at the sister chromatid interaction step.

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Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase

Cited by 295 publications

References 86 publications

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

The Escherichia coli Tus–Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

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